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Intracoronary Radiation

2000; Lippincott Williams & Wilkins; Volume: 101; Issue: 4 Linguagem: Inglês

10.1161/01.cir.101.4.350

1524-4539

David O. Williams, Barry L. Sharaf,

Cardiac Imaging and Diagnostics

HomeCirculationVol. 101, No. 4Intracoronary Radiation Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBIntracoronary Radiation It Keeps on Glowing David O. Williams and Barry L. Sharaf David O. WilliamsDavid O. Williams From the Division of Cardiology, Department of Medicine, Rhode Island Hospital, Brown University, School of Medicine, Providence, RI. and Barry L. SharafBarry L. Sharaf From the Division of Cardiology, Department of Medicine, Rhode Island Hospital, Brown University, School of Medicine, Providence, RI. Originally published1 Feb 2000https://doi.org/10.1161/01.CIR.101.4.350Circulation. 2000;101:350–351Stents are now used routinely for catheter-based coronary revascularization procedures. Early clinical trials of stents demonstrated reduced rates of angiographic restenosis compared with balloon angioplasty alone.123 In a registry analysis of 1403 patients, 64% of whom were treated with stents, the need for repeat revascularization was 39% less than in a similar cohort having coronary intervention in the prestent era.4 In addition to enhancing the durability of coronary angioplasty, stents appear to improve its safety. As stent usage has increased further, the rates of abrupt artery closure and complex dissection associated with catheter-based interventions have declined progressively from 2% to 1% and from 11% to 5%, respectively.5 Stents have also expanded the pool of patients suitable for nonsurgical revascularization. Lesions that are treated currently are longer and are located in more tortuous and smaller arteries.Although stents substantially reduce the relative risk for lesion recurrence, the absolute chance of experiencing restenosis is still significant. Furthermore, when restenosis occurs within a stent, conventional treatments are of limited value, as repeat in-stent restenosis is observed in 54% to 66% of patients.678 There have been many attempts to improve on these results by placing a new stent within the original stent and supplementing repeat balloon angioplasty with excimer laser, high-speed rotational atherectomy and directional atherectomy. None of these strategies, however, have proved particularly successful.Studies using intracoronary ultrasound have demonstrated that in-stent restenosis is due to neointimal tissue proliferation.9 Considering that radiation has been effective in the treatment of other hyperplastic disorders, both benign and malignant, investigators speculated that locally applied radiation might be useful for the treatment of restenosis, especially in-stent restenosis. Accordingly, intracoronary brachytherapy, using both β- and γ-emitting sources, has been evaluated intensively.678101112 Several randomized clinical trials have focused on in-stent restenosis. Data are available from 3 studies that used 192Ir.678 The results are remarkably consistent and demonstrate impressive benefit, with treatment effects in the range of 50% to 60%. β-Sources have also been evaluated for in-stent restenosis, as well as for de novo and restenotic lesions not previously stented.101112 Preliminary observational results are similarly encouraging.Although we have had considerable experience with intracoronary brachytherapy in the short-term, our knowledge of late patient outcome is limited. Natural questions relate to the sustained effectiveness of intracoronary brachytherapy and its safety. Does brachytherapy provide permanent protection against restenosis, or is the process merely delayed? Is intracoronary brachytherapy harmful? Will it result in myocardial damage and dysfunction with eventual heart failure? Will we see pericardial disease? Does brachytherapy accelerate atherosclerosis in neighboring coronary arteries? Do treated arteries undergo degeneration or expansion or form aneurysms?13 In this issue of Circulation, Teirstein and coauthors14 add important information to help answer these questions. They report the 3-year clinical and coronary angiographic outcome of patients enrolled in a trial that initially established the benefits of intracoronary brachytherapy in treating restenosis.Several aspects of the Teirstein report are worth noting. First, the study was composed of patients with restenosis; some had been treated previously with a stent. Thus, the results of the trial apply to a mixed group of patients presenting with restenosis rather than just to a specific subset. Some had in-stent restenosis, and some did not.For these patients, the cumulative 3-year rate of target-lesion revascularization was substantially lower among those receiving brachytherapy (15.4%) than among those treated by conventional techniques (48.3%). The restenosis rate for radiated patients having follow-up coronary angiography was 33.3% compared with 63.6% for controls. This independent, parallel assessment further validates treatment effectiveness. Also, when target-lesion revascularization occurred in either group, it nearly always occurred within the first 6 months. Thus, the effectiveness of intracoronary brachytherapy was sustained over the 3-year period. There was no evidence of delayed restenosis in treated patients. Importantly, the benefits of radiation remained substantial even when restenosis at the edges of the original lesions was classified as a treatment failure.Second, adverse clinical events suggestive of serious myocardial or arterial damage from radiation were not identified. Review of hospitalizations for cardiac causes did not reveal the development of excessive heart failure or pericarditis. Furthermore, follow-up coronary angiography did not detect any coronary aneurysms or pseudoaneurysms among treated patients.Third, there was considerable revascularization for lesions other than the original restenotic lesions. It is not likely that radiation was responsible for these events, because the rates of nonindex lesion revascularization were similar in both the radiated and control groups. More likely is the explanation that coronary artery disease is a progressive illness, and measures to attenuate disease progression are required as adjuncts to revascularizations.15Fourth, a 0.37-mm decline in the mean value of minimal lumen diameter was observed in 17 irradiated patients but not in 10 control subjects. The significance of this observation is unclear. Both the magnitude of this change and the size of the group in which it was observed were small. Additional observations from larger patient cohorts will be needed for clarification.Although this report helps to address several important questions about intracoronary brachytherapy, the small number of patients in the trial, the form of brachytherapy used, and the types of patients enrolled leave many additional, important questions unanswered. For example, we need to know more about each specific patient subgroup, including those who receive brachytherapy with or without a prior stent and with or without a new stent. Late stent thrombosis has been described recently. This condition, often presenting as unstable angina or acute myocardial infarction, appears to be strongly associated with the use of radiation, a fresh stent, and discontinuation of antiplatelet therapy. We fully expect to overcome this disorder and need to demonstrate this accomplishment convincingly. Because β-radiation is more "user friendly" and likely to be adopted with enthusiasm, we need to learn about its long-term effects. Finally, how long is long term? Given the 5 to 15 years that may be required to detect certain cardiac effects of radiation,16 we need to extend our observations after intracoronary brachytherapy beyond 3 years.We appreciate the efforts of Teirstein and colleagues in the field of coronary brachytherapy for their initial and continued research. These efforts have clearly demonstrated that intracoronary brachytherapy can reduce the incidence of restenosis in both the short and long term and that it is of particular value to patients with in-stent restenosis for whom there is no effective catheter-based alternative. Although we are reassured by the safety data available through 3 years of follow-up, we encourage continued surveillance by early investigators to further augment our understanding of this very important and potent therapy.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.The authors wish to thank Arlene S. Grant for assisting in the preparation of this manuscript.FootnotesCorrespondence to David O. Williams, MD, Division of Cardiology, APC 814, Rhode Island Hospital, 593 Eddy St, Providence, RI 02903. E-mail [email protected] References 1 Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, Detre K, Veltri L, Ricci D, Nobuyoshi M, Cleman M, Heuser R, Almond D, Teirstein PS, Fish RD, Colombo A, Brinker J, Moses J, Shaknovich A, Hirshfeld J, Bailey S, Ellis S, Rake R, Goldberg S, for the Stent Restenosis Study Investigators. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med.1994; 331:496–501.CrossrefMedlineGoogle Scholar2 Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P, Belardi J, Sigwart U, Colombo A, Guy JJ, van den Heuvel P, Delcan J, Morel M, for the Benestent Study Group. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med.1994; 331:489–495.CrossrefMedlineGoogle Scholar3 Serruys PW, van Hout B, Connier H, Legrand V, Garcia E, Macaya C, Sousa E, Van der Giessen W, Colombo A, Seabra-Gomes R, Kiemeneij F, Roygrok P, Ormistron J, Emanuelson H, Fajadet J, Haude M, Klugmann S, Morel MA. Randomized comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II). Lancet.1998; 352:673–681.CrossrefMedlineGoogle Scholar4 Williams DO, Yeh W, Holubkov R, Detre KM, Faxon DP, Slater JN, Cowley MJ, Stanek V. Preliminary report from the new NHLBI Dynamic Registry for percutaneous coronary interventions: a comparison to the 1985–86 PTCA registry. Circulation. 1998;98(suppl I):I-197. Abstract.Google Scholar5 Williams DO, Detre KM, Vlachos H, Kelsey SF, Cohen HA, Holmes DR, King SB III. Changes in the practice of contemporary percutaneous coronary intervention: a comparison of enrollment waves in the Dynamic Registry. Circulation. 1999;100(suppl I):I-512. Abstract.Google Scholar6 Teirstein PS, Massullo V, Jani S, Popma JJ, Mintz GS, Russo RJ, Schatz RA, Guarneri EM, Steuterman S, Morris NB, Leon MB, Tripuraneni P. Catheter-based radiotherapy to inhibit restenosis after coronary stenting. N Engl J Med.1997; 336:1697–1703.CrossrefMedlineGoogle Scholar7 Waksman R, White LR, Chan RC, Porrazo MS, Bass BG, Satler LF, Kent KM, Geirlach LM, Mehran R, Murphy M, Mintz GS, Leon MB. Intracoronary radiation therapy for patients with in-stent restenosis: 6 month follow-up of a randomized clinical study. Circulation. 1998;98(suppl I):I-651. Abstract.Google Scholar8 Leon MB, Moses JW, Lansky AJ, Wong SC, Nawaz DM, Whitlow PL, Fish DR, Kluck B, Gorgianni J, Kuntz RE, Teirstein PS. Intracoronary gamma radiation for the prevention of recurrent in-stent restenosis: final results from the Gamma-1 Trial. Circulation. 1999;100(suppl I):I-75. Abstract.Google Scholar9 Hoffman R, Mintz GS, Dussaillant GR, Popma JJ, Pichard AD, Satler LF, Kent KM, Griffin J, Leon MB. Patterns and mechanisms of in-stent restenosis: a serial intravascular ultrasound study. Circulation.1996; 94:1247–1254.CrossrefMedlineGoogle Scholar10 King SB III, Williams DO, Chougule P, Klein JL, Waksman R, Hilstead R, Macdonald J, Anderberg K, Crocker IR. Endovascular β-radiation to reduce restenosis after coronary balloon angioplasty: results of the Beta Energy Restenosis Trial (BERT). Circulation.1998; 97:2025–2030.CrossrefMedlineGoogle Scholar11 Raizner AE, Oesterle SN, Waksman R, Chiu JK, Tate D, White LR, Levy GV, Kaluza GL, Ali NM. Inhibition of restenosis with Beta-emitting radiation (32P): the final report of the PREVENT Trial. Circulation. 1999;100(suppl I):I-75. Abstract.Google Scholar12 Waksman R, White LR, Chan RC, Mehran R, Bhargava B, Lansky AJ, Pichard AD, Stone GW, Leon MB. Intracoronary beta radiation therapy for patients with in-stent restenosis: the 6 months clinical and angiographic results. Circulation. 1999;100(suppl I):I-75. Abstract.Google Scholar13 Condado JA, Waksman R, Gurdiel O, Espinosa R, Gonzalez J, Berger B, Villoria G, Acquatella H, Crocker IR, Seung KB, Liprie SF. Long-term angiographic and clinical outcome after percutaneous transluminal coronary angioplasty and intracoronary radiation therapy in humans. Circulation.1997; 96:727–732.CrossrefMedlineGoogle Scholar14 Teirstein PS, Massullo V, Jani S, Popma JJ, Russo RJ, Schatz RA, Guarneri EM, Steuterman S, Sirkin K, Cloutier DA, Leon MB, Tripuraneni P. Three-year clinical and angiographic follow-up after intracoronary radiation: results of a randomized clinical trial. Circulation.2000; 101:360–365.CrossrefMedlineGoogle Scholar15 Pitt B, Waters D, Brown WV, van Bove AJ, Schwartz L, Title LM, Eisenberg D, Shurzinske L, McCormick LS, for the Atorvastatin versus Revascularization Treatment Investigators. Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. N Engl J Med.1999; 341:70–76.CrossrefMedlineGoogle Scholar16 Gottdiener JS, Katin MJ, Borer JS, Bacharach SL, Green MV. Late cardiac effects on therapeutic mediastinal irradiation: assessment by echocardiography and radionuclide angiography. N Engl J Med.1983; 308:569–572.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Lima X, Seidler E, Lima H and Kimball A (2009) Long-term safety of biologics in dermatology, Dermatologic Therapy, 10.1111/j.1529-8019.2008.01212.x, 22:1, (2-21), Online publication date: 1-Jan-2009. Iftimia I, Devlin P, Chin L, Baron J and Cormack R (2003) GAF film dosimetry of a tandem positioned β-emitting intravascular brachytherapy source train, Medical Physics, 10.1118/1.1573206, 30:6, (1004-1012), Online publication date: 21-May-2003. Sehgal V, Li Z, Palta J, Smith K and Bolch W (2002) Application of imaging-derived parameters to dosimetry of intravascular brachytherapy sources: Perturbation effects of residual plaque burden, Medical Physics, 10.1118/1.1485053, 29:7, (1580-1589), Online publication date: 24-Jun-2002. Sehgal V, Li Z, Palta J and Bolch W (2001) Dosimetric effect of source centering and residual plaque for β-emitting catheter based intravascular brachytherapy sources, Medical Physics, 10.1118/1.1406520, 28:10, (2162-2171), Online publication date: 1-Oct-2001. Rectenwald J, Pretus H, Seeger J, Huber T, Mendenhall N, Zlotecki R, Palta J, Feng Li Z, Hook S, Sarac T, Burress Welborn M, Klingman N, Abouhamze Z and Keith Ozaki C (2001) External-Beam Radiation Therapy for Improved Dialysis Access Patency: Feasibility and Early Safety, Radiation Research, 10.1667/0033-7587(2001)156[0053:EBRTFI]2.0.CO;2, 156:1, (53-60), Online publication date: 1-Jul-2001. February 1, 2000Vol 101, Issue 4 Advertisement Article InformationMetrics Copyright © 2000 by American Heart Associationhttps://doi.org/10.1161/01.CIR.101.4.350 Originally publishedFebruary 1, 2000 KeywordsradiotherapyrevascularizationEditorialsrestenosiscoronary angioplastystentsPDF download Advertisement